Coronary artery bypass and graft (CABG) is a common procedure for restoring blood flow to cardiac regions made ischemic due to blockage of the coronary arteries via atherosclerotic lesions. While the CABG procedure is commonly performed, there are still problems associated with it. One problem is that in order to perform the bypass, the surgeon requires a still field which means that the heart must be stopped. In order to accomplish this, the patient must be placed on a machine which pumps and oxygenates the blood (pump-oxygenator or heat-lung pump). Upon completion of the CABG, the heart must then be restarted. Since coronary blood flow is cut off during the procedure, the heart may undergo varying degrees of ischemia which may impair the ability of the heart to resume normal function. Thromboxane A.sub.2 (TXA) antagonists have been found to improve this return of function in various models of short-term myocardial ischemia simulating CABG, Grover, G. J., et al., "Thromboxane A.sub.2 Antagonist and Diltiazem Induced Enhancement of Contractile Function: The Effect of Timing of Treatment" (Submitted for publication). One other serious problem encountered during this procedure is the severe platelet loss due to the heart-lung pump, McKenna, R. F., et al., "The Hemostatic Mechanism after Open-heart surgery", J. Thorac. Cardiovasc. Surg. 70:298, 1975. Thus, to reduce post-surgical bleeding, these patients must be transfused with platelet rich blood with its concomitant risk of infections.
It would thus be an advance in the art to find a means of reducing this platelet loss without an untoward effect on the CABG procedure itself. Although the nature of the platelet loss is not fully understood, it is believed that it is due to contact with the synthetic surfaces of the extracorporeal perfusion circuit. This interaction is associated with the release of TXA which is a powerful platelet aggregating agent, Ogletree, M. L., "Overview of Physiological and Pathophysiological Effects of Thromboxane A.sub.2 ", Fed. Proc. 46:133, 1987. While aspirin has been found to be ineffective in inhibiting platelet loss in models of CABG, Addonizio, V. P., et al., "Thromboxane Synthesis and Platelet Secretion during Cardiopulmonary Bypass with Bubble Oxygenator", J. Thorac. Cardiovasc. Surg. 79:91, 1980, prostacyclin significantly reduces platelet loss in similar models, Wonder, T., et al., "Preservation of Platelet Number and Function During Extracorporeal Membrane Oxygenation (ECMO) by Regional Infusion of PGI.sub.2 ", Circulation 58:II-207, 1978. The problem with administration of prostacyclin to the patient is that it results in a severe and dose-dependent systemic hypotension. Thus, a compound which could reduce platelet loss by itself without untoward hemodynamic consequences or combined with prostacyclin in such a manner as to minimize its hypotensive effects would be important in improving the CABG procedure and other procedures that involve extracorporeal circulation of the blood.